Buprenorphine (BUP) dose-dependently blocks the behavioral effects of hydromorphone (HYD) for periods up to 24 hours. The present double-blind study examined the duration of this blockade for up to 96 hours across a 24, 48, and 72 hour BUP dosing schedule (BDS). 8 male, opiod dependent outpatients abstinent from illicit opiods and maintained on either 4 or 8 mg/70kg, s.1. BUP (n=4 group) were exposed to each dosing schedule in a mixed sequence and participated in 10 laboratory sessions. During the 24 , 48, and 72 hour BDS subjects received their maintenance dose, 2x their maintenance dose, 3x their maintenance dose every 24, 48, 72 hours respectively. Under the 24, 48, and 72 hour BDS, subjects received placebo on the interposed days. In laboratory sessions, subjects received sequential s.c. injections of saline, 6 and 12/70Kg HYD at 90 minute intervals using a cumulative dosing procedure. As a positive control for HYD effects without BUP blockade, one of these sessions occurred following a three day exposure to 2mg/79Kg of BUP; placebo BUP was not used for ethical reasons. A blood sample was drawn before and physiology and behavior assessed throughout each session. As expected, HYD produced the greatest effects under the 2 mg BUP condition. In the 8 mg group, BUP blocked HYDs effects on observer and subject rated measures of opioid agonist effects in a dose related manner for up to 48 hours under the 24, 48, 72 hour BDS. BUP blockade of the cumulative 18 mg HYD challenge dissipated by 72 hours. These effects were not replicated in the 4 mg subject group and may reflect differences in BUP metabolism as suggested by plasma BUP levels. BUP did not block physiological responses to HYD in either the 4 or 8 mg group. Overall the data suggest that the 24, 48 hour BDS maintain effective blockade of exogeneous opioids for up to 48 hours in patients maintained on an 8 mg sublingual BUP dose. However since blockade may be compromised during the 72 hour BDS, the 72 hour schedule may not be restricted to patients with appreciable periods of abstinence from street opioids. During 12/1/95-11/30/96 follow up blood samples were drawn from 6 subjects and the study is now complete.